Anion Recognition by Aliphatic Helical Oligoureas

Anion binding properties of neutral helical foldamers consisting of urea type units in their backbone have been investigated. ¹H NMR titration studies in various organic solvents including DMSO suggest that the interaction between aliphatic oligoureas and anions (CH₃COO^?, H₂PO₄^?, Cl^?) is site‐specific, as it largely involves the urea NHs located at the terminal end of the helix (positive pole of the helix), which do not participate to the helical intramolecular hydrogen‐bonding network. This mode of binding parallels that found in proteins in which anion‐binding sites are frequently found at the N‐terminus of an α‐helix. ¹H NMR studies suggest that the helix of oligoureas remains largely folded upon anion binding, even in the presence of a large excess of the anion. This study points to potentially useful applications of oligourea helices for the selective recognition of small guest molecules.     

Hydrogen bonding by alcohols and amines

The pure base calorimetric method has been used to determine the enthalpies of hydrogen bond complex formation between aliphatic amines and alcohols. The enthalpies of complexation for the series methanol-n-butanol bonding with triethylamine increase with decreasing alkyl chain length in accordance with the electron donating properties of alkyl groups. Unexpectedly, the enthalpies for the complexes of n-butanol with tributylamine, tripropylamine, and triethylamine increase with decreasing alkyl chain length.Primary and secondary amines form hydrogen bonded complexes with n-butanol in which the amine protons form an NH···O bond with the alcohol and the alcohol hydroxyl proton donates a proton to the amine nitrogen. The difference in enthalpy of complex formation between tertiary amines and secondary amines is largely accounted for by the involvement of the amine proton of the secondary amine. Primary amines, like secondary amines, donate only one proton to the complex with n-butanol but have a larger complex enthalpy than secondary amines probably because of steric hindrance and differences in basicity.     

Enthalpy of cooperative hydrogen bonding in complexes of tertiary amines with aliphatic alcohols: Calorimetric study

The work is devoted to the investigation of thermodynamics of specific interaction of the tertiary aliphatic and aromatic amines with associated solvents as which aliphatic alcohols were taken. Solution enthalpies of aliphatic alcohols in amines (tri-n-propylamine, 2-methylpyridine, 3-methylpyridine, N-methylimidazole) as well as amines in alcohols were measured at infinite dilution. The enthalpies of specific interaction (H-bonding) in systems studied were determined based on experimental data. The enthalpies of specific interaction of amines in aliphatic alcohols significantly lower than the enthalpies of hydrogen bonding in complexes amine–alcohol of 1:1 composition determined in base media due to the reorganization of aliphatic alcohols as solvents. The determination of solvent reorganization contribution makes possible to define the hydrogen bonding enthalpies of amines with clusters of alcohols. Obtained enthalpies of hydrogen bonding in multi-particle complexes are sensitive to the influence of cooperative effect. It was shown, that hydrogen bond cooperativity factors in multi-particle complexes of alcohols with amines are approximately equal for all alcohols when pyridines and N-methylimidazole as solutes are used. At the same time, H-bonding cooperativity factors in complexes of trialkylamines with associative species of alcohols decrease with increasing of alkyl radical length in alcohol and amine molecules.This work shows that the thermodynamic functions of specific interaction of solutes with associated solvents cannot be described using the H-bond parameters for the complexes of 1:1 composition.     

Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox,HAT, and Nickel Catalysis

The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α‐hydroxy C−H bonds. This approach employs zinc‐mediated alcohol deprotonation to activate α‐hydroxy C−H bonds while simultaneously suppressing C−O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn‐based Lewis acids also deactivates other hydridic bonds such as α‐amino and α‐oxy C−H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3‐step synthesis of the drug Prozac exemplifies the utility of this new method.     

Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox,HAT, and Nickel Catalysis

The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α‐hydroxy C?H bonds. This approach employs zinc‐mediated alcohol deprotonation to activate α‐hydroxy C?H bonds while simultaneously suppressing C?O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn‐based Lewis acids also deactivates other hydridic bonds such as α‐amino and α‐oxy C?H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3‐step synthesis of the drug Prozac exemplifies the utility of this new method.     

Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

A structural feature of hydrogen bonding chains found in the crystals of trifluoromethylated amino alcohols is reported. Hydrogen bondings of 3-(N,N-dialkylamino)-1,1,1-trifluoro-2-propanols construct chiral spiral hydrogen bonding chains. Lone pairs on the nitrogen atoms of the amino alcohols participate in two hydrogen bondings. Detailed structural analysis of the hydrogen bonds of the 3-(N,N-dimethylamino)-1,1,1-trifluoro-2-propanol suggested that the chain built up with alternating intermolecular-medium and intramolecular-weak hydrogen bonds. The medium intermolecular hydrogen bond, which transfers a proton from the hydroxy group to the amino nitrogen, would make a tentative zwitterionic form of the molecule. Then, electrostatic attraction between the charges in the zwitterion centers induced a weak intramolecular hydrogen bond.     

Reactions in the Photocatalytic Conversion of Tertiary Alcohols on Rutile TiO2(110)

According to textbooks, tertiary alcohols are inert towards oxidation. The photocatalysis of tertiary alcohols under highly defined vacuum conditions on a titania single crystal reveals unexpected and new reactions, which can be described as disproportionation into an alkane and the respective ketone. In contrast to primary and secondary alcohols, in tertiary alcohols the absence of an α‐H leads to a C?C‐bond cleavage instead of the common abstraction of hydrogen. Surprisingly, bonds to methyl groups are not cleaved when the alcohol exhibits longer alkyl chains in the α‐position to the hydroxyl group. The presence of platinum loadings not only increases the reaction rate but also opens up a new reaction channel: the formation of molecular hydrogen and a long‐chain alkane resulting from recombination of two alkyl moieties. This work demonstrates that new synthetic routes may become possible by introducing photocatalytic reaction steps in which the co‐catalysts may also play a decisive role.     

Tandem Pd/Au‐Catalyzed Route to α‐Sulfenylated Carbonyl Compounds from Terminal Propargylic Alcohols and Thiols

An efficient and highly atom‐economical tandem Pd/Au‐catalyzed route to α‐sulfenylated carbonyl compounds from terminal propargylic alcohols and thiols has been developed. This one‐step procedure has a wide substrate scope with respect to substituents at the α‐position of the alcohol. Both aromatic and aliphatic thiols generated the α‐sulfenylated carbonyl products in good to excellent yields. A mechanism is proposed in which the reaction proceeds through a Pd‐catalyzed regioselective hydrothiolation at the terminal triple bond of the propargyl alcohol followed by an Au‐catalyzed 1,2‐hydride migration.     

Enthalpy of cooperative hydrogen bonding in the complexes of triethyl- and tri-<Emphasis Type="Italic">n</Emphasis>-butylamines with alcohols: Effect of the alkyl chain length

The measurements of enthalpies of triethylamine and tri-n-butylamine dissolution in aliphatic alcohols and, vice versa, of aliphatic alcohols in amines were carried out. Enthalpies of specific interactions in the studied systems were calculated. The enthalpy of specific interaction determined in the alcohol medium, are significantly less than those obtained at dissolving alcohols in amines. The mechanism of specific interaction of amines with alcohols is discussed. Enthalpies of cooperative hydrogen bonds of tertiary amines with alcohol clusters are calculated. The dependences between the enthalpies of hydrogen bond and the spatial structure of interacting molecules are revealed.     

Helix Nucleation by the Smallest Known α‐Helix in Water

Cyclic pentapeptides (e.g. Ac‐(cyclo‐1,5)‐[KAXAD]‐NH₂; X=Ala, 1 ; Arg, 2 ) in water adopt one α‐helical turn defined by three hydrogen bonds. NMR structure analysis reveals a slight distortion from α‐helicity at the C‐terminal aspartate caused by torsional restraints imposed by the K(i)–D(i+4) lactam bridge. To investigate this effect on helix nucleation, the more water‐soluble 2 was appended to N‐, C‐, or both termini of a palindromic peptide ARAARAARA (≤5 % helicity), resulting in 67, 92, or 100 % relative α‐helicity, as calculated from CD spectra. From the C‐terminus of peptides, 2 can nucleate at least six α‐helical turns. From the N‐terminus, imperfect alignment of the Asp5 backbone amide in 2 reduces helix nucleation, but is corrected by a second unit of 2 separated by 0–9 residues from the first. These cyclic peptides are extremely versatile helix nucleators that can be placed anywhere in 5–25 residue peptides, which correspond to most helix lengths in protein–protein interactions.     

A Study of the Solvation Structure of l‐Leucine in Alcohol–Water Binary Solvents through Molecular Dynamics Simulations and FTIR and NMR Spectroscopy

The solvation structures of l ‐leucine (Leu) in aliphatic‐alcohol–water and fluorinated‐alcohol–water solvents are elucidated for various alcohol contents by using molecular dynamics (MD) simulations and IR, and ¹H and ¹³C NMR spectroscopy. The aliphatic alcohols included methanol, ethanol, and 2‐propanol, whereas the fluorinated alcohols were 2,2,2‐trifluoroethanol and 1,1,1,3,3,3‐hexafluoro‐2‐propanol. The MD results show that the hydrophobic alkyl moiety of Leu is surrounded by the alkyl or fluoroalkyl groups of the alcohol molecules. In particular, TFE and HFIP significantly solvate the alkyl group of Leu. IR spectra reveal that the Leu C?H stretching vibration blueshifts in fluorinated alcohol solutions with increasing alcohol content, whereas the vibration redshifts in aliphatic alcohol solutions. When the C?H stretching vibration blueshifts in the fluorinated alcohol solutions, the hydrogen and carbon atoms of the Leu alkyl group are magnetically shielded. Consequently, TFE and HFIP molecules may solvate the Leu alkyl group through the blue‐shifting hydrogen bonds.     

Intramolecular Hydrogen Bonds in Low‐Molecular‐Weight Polyethylene Glycol

We used static DFT calculations to analyze, in detail, the intramolecular hydrogen bonds formed in low‐molecular‐weight polyethylene glycol (PEG) with two to five repeat subunits. Both red‐shifted O?H???O and blue‐shifting C?H???O hydrogen bonds, which control the structural flexibility of PEG, were detected. To estimate the strength of these hydrogen bonds, the quantum theory of atoms in molecules was used. Car–Parrinello molecular dynamics simulations were used to mimic the structural rearrangements and hydrogen‐bond breaking/formation in the PEG molecule at 300 K. The time evolution of the H???O bond length and valence angles of the formed hydrogen bonds were fully analyzed. The characteristic hydrogen‐bonding patterns of low‐molecular‐weight PEG were described with an estimation of their lifetime. The theoretical results obtained, in particular the presence of weak C?H???O hydrogen bonds, could serve as an explanation of the PEG structural stability in the experimental investigation.     

Intramolecular OH···π interactions in alkenols and alkynols

The vibrational overtone spectra of propargyl alcohol (prop-2-yn-1-ol, PA), allyl alcohol (prop-2-en-1-ol, AA), propargyl carbinol (but-3-yn-1-ol, PC) and allyl carbinol (but-3-en-1-ol, AC) were recorded with intracavity laser photoacoustic spectroscopy (ICL-PAS) in the Δv(OH) = 3, 4 and 5 regions for propargyl alcohol and allyl alcohol and in the Δv(OH) = 4 and 5 regions for propargyl carbinol and allyl carbinol. Local mode anharmonic oscillator calculations were performed with explicitly correlated coupled cluster methods to guide spectral assignment. Atoms in molecules (AIM) and non-covalent interactions (NCI) calculations were carried out to analyze the interactions between the OH-group and the π-electrons of the carbon-carbon multiple bonds. We ascertain the effect of the carbon chain length and saturation on the conformation and spectroscopy of the four alcohols in relation to intramolecular hydrogen bonding interactions.     

Effect of temperature and water content on the structure of 1,2-propanediol and 1,3-propanediol: Near-infrared spectroscopic study

Effect of temperature and water content on the structure of 1,2-propanediol (12PD) and 1,3-propanediol (13PD) in the liquid phase has been studied by Fourier-transform near-infrared (FT-NIR) spectroscopy. In addition, the spectra of both diols in CCl₄ solutions at various concentrations were measured. The experimental spectra were analyzed by two-dimensional (2D) correlation approach and chemometric methods. The present results give no evidence that 12PD form the intramolecular hydrogen bonding. In contrast, significant amounts of 13PD molecules in diluted CCl₄ solution is involved in the intramolecular hydrogen bonding. At higher concentrations the intramolecular hydrogen bonds are broken and replaced by the intermolecular ones. The structure of pure liquid propanediols is determined by the intermolecular hydrogen bonding. Unlike for monohydroxyl alcohols, addition of water to propanediols leads to faster temperature-induced breaking of the hydrogen-bonded associates. However, variation of water content at constant temperature does not influence the structure of both diols. In this respect behavior of propanediols is similar to that of the monohydric alcohols. The molecules of water in the mixtures are hydrogen bonded to the diols and act as a double proton donor. This bonding appears to be stronger than that in bulk water.     

Cooperative Catalysis of Metal and O?H⋅⋅⋅O/sp3‐C?H⋅⋅⋅O Two‐Point Hydrogen Bonds in Alcoholic Solvents: Cu‐Catalyzed Enantioselective Direct Alkynylation of Aldehydes with Terminal Alkynes

Catalyst–substrate hydrogen bonds in artificial catalysts usually occur in aprotic solvents, but not in protic solvents, in contrast to enzymatic catalysis. We report a case in which ligand–substrate hydrogen‐bonding interactions cooperate with a transition‐metal center in alcoholic solvents for enantioselective catalysis. Copper(I) complexes with prolinol‐based hydroxy amino phosphane chiral ligands catalytically promoted the direct alkynylation of aldehydes with terminal alkynes in alcoholic solvents to afford nonracemic secondary propargylic alcohols with high enantioselectivities. Quantum‐mechanical calculations of enantiodiscriminating transition states show the occurrence of a nonclassical sp³‐C? H???O hydrogen bond as a secondary interaction between the ligand and substrate, which results in highly directional catalyst–substrate two‐point hydrogen bonding.     

Effects of sugar ring puckering, anti-syn interconversion and intramolecular interactions on N-glycosidic bond cleavage in 3-methyl-2��-deoxyadenosine and 2��-deoxyadenosine

The effects of structural parameters and intramolecular interactions on N-glycosidic bond length in 3-methyl-2??- deoxyadenosine (3MDA) and 2??-deoxyadenosine (DA) were investigated employing quantum mechanical methods. All calculations were performed at B3LYP/6-311++G** level in the gas phase. The N-glycosidic bond length strongly depends on sugar configuration; it is shorter in syn conformation relative to anti in many cases where they have the same sugar ring configuration. The sugar conformation can influence the N-glycosidic bond through interaction with the O4?? atom. The impact of intramolecular improper hydrogen bonds and H-H bonding interactions on N-glycosidic bond length was investigated in DA and 3MDA and their modeled structures. Improper hydrogen bonds decrease N-glycosidic bond length while H-H bonding interactions increase it.     

Charge‐Induced Secondary Structure Transformation of Amyloid‐Derived Dipeptide Assemblies from β‐Sheet to α‐Helix

Secondary structures such as α‐helix and β‐sheet are the major structural motifs within the three‐dimensional geometry of proteins. Therefore, structure transitions from β‐sheet to α‐helix not only can serve as an effective strategy for the therapy of neurological diseases through the inhibition of β‐sheet aggregation but also extend the application of α‐helix fibrils in biomedicine. Herein, we present a charge‐induced secondary structure transition of amyloid‐derived dipeptide assemblies from β‐sheet to α‐helix. We unravel that the electrostatic (charge) repulsion between the C‐terminal charges of the dipeptide molecules are responsible for the conversion of the secondary structure. This finding provides a new perspective to understanding the secondary structure formation and transformation in the supramolecular organization and life activity.     

Stability and Unfolding Mechanism of the N‐terminal β‐Hairpin from [2Fe‐2S] Ferredoxin I by Molecular Dynamics Simulations

The stability and unfolding mechanism of the N‐terminal β‐hairpin of the [2Fe‐2S] ferredoxin I from the blue‐green alga Aphanothece sacrum in pure methanol, 40% (v/v) methanol‐water, and pure water systems were investigated by 10 ns molecular dynamics simulations under periodic boundary conditions. The β‐hairpin was mostly in its native‐like state in pure methanol, whereas it unfolds dramatically following the ‘zip‐up’ mechanism when it was placed in pure water. Both interstrand and inside‐turn hydrogen bonds account for the stability of the β‐hairpin in its native‐like conformation, whereas hydrophobic interactions among nonpolar side chains are responsible for maintaining its stable loop‐like intermediate structures in 40% (v/v) methanol‐water. Reducing solvent polarity seems to increase the stability of the β‐hairpin in its native‐like structure. Methanol is likely to mimic the partially hydrophobic environment around the N‐terminal β‐hairpin by the subsequent α‐helix.     

The Double‐Faced Nature of Hydrogen Bonding in Hydroxy‐Functionalized Ionic Liquids Shown by Neutron Diffraction and Molecular Dynamics Simulations

We characterize the double‐faced nature of hydrogen bonding in hydroxy‐functionalized ionic liquids by means of neutron diffraction with isotopic substitution (NDIS), molecular dynamics (MD) simulations, and quantum chemical calculations. NDIS data are fit using the empirical potential structure refinement technique (EPSR) to elucidate the nearest neighbor H???O and O???O pair distribution functions for hydrogen bonds between ions of opposite charge and the same charge. Despite the presence of repulsive Coulomb forces, the cation–cation interaction is stronger than the cation–anion interaction. We compare the hydrogen‐bond geometries of both “doubly charged hydrogen bonds” with those reported for molecular liquids, such as water and alcohols. In combination, the NDIS measurements and MD simulations reveal the subtle balance between the two types of hydrogen bonds: The small transition enthalpy suggests that the elusive like‐charge attraction is almost competitive with conventional ion‐pair formation.